Chaperone-Mediated Autophagy Controls Proteomic and Transcriptomic Pathways to Maintain Glioma Stem Cell Activity.

Chaperone-mediated autophagy (CMA) is a homeostatic process essential for the lysosomal degradation of a selected subset of the proteome. CMA activity directly depends on the levels of LAMP2A, a critical receptor for CMA substrate proteins at the lysosomal membrane. In glioblastoma (GBM), the most common and aggressive brain cancer in adulthood, high levels of LAMP2A in the tumor and tumor-associated pericytes have been linked to temozolomide resistance and tumor progression. However, the role of LAMP2A, and hence CMA, in any cancer stem cell type or in glioblastoma stem cells (GSC) remains unknown. In this work, we show that LAMP2A expression is enriched in patient-derived GSCs, and its depletion diminishes GSC-mediated tumorigenic activities. Conversely, overexpression of LAMP2A facilitates the acquisition of GSC properties. Proteomic and transcriptomic analysis of LAMP2A-depleted GSCs revealed reduced extracellular matrix interaction effectors in both analyses. Moreover, pathways related to mitochondrial metabolism and the immune system were differentially deregulated at the proteome level. Furthermore, clinical samples of GBM tissue presented overexpression of LAMP2, which correlated with advanced glioma grade and poor overall survival. In conclusion, we identified a novel role of CMA in directly regulating GSCs activity via multiple pathways at the proteome and transcriptome levels. SIGNIFICANCE: A receptor of chaperone-mediated autophagy regulates glioblastoma stem cells and may serve as a potential biomarker for advanced tumor grade and poor survival in this disease.

Subluxación atlanto-axoidea secundaria a absceso retrofaríngeo en el adulto (síndrome de Grisel). Revisión de la literatura a propósito de un caso clínico / Atlantoaxial subluxation secondary to retropharyngeal abcess in adults (Grisel's syndrome). Review of literature about a clinical case

El síndrome de Grisel (SG) se trata de una subluxación atlanto-axoidea no traumática producida luego de un proceso inflamatorio, infeccioso o posquirúrgico de la región superior de cuello. Es una complicación característica, aunque actualmente infrecuente, de la faringitis bacteriana aguda en la edad pediátrica. La presentación en adultos es aún más infrecuente y requiere un manejo específico. Presentamos el caso de una paciente de 68 años con antecedentes de leucemia mieloide crónica, que se presentó con poliartritis infecciosa, cervicalgia, tortícolis e impotencia cervical. La radiografía, la TC y la RM cervical demostraron una subluxación C1-C2 adyacente a un absceso faríngeo, diagnosticándose un SG. Al finalizar el tratamiento antibioticoterápico, la paciente debió ser intervenida quirúrgicamente debido al fracaso de la reducción cerrada. Debido a su incidencia tan baja, no existen guías clínicas para el manejo de estos pacientes; la colaboración interdisciplinaria es fundamental para establecer el diagnóstico oportuno que permita instaurar el tratamiento conservador y prevenir tanto la cirugía como las complicaciones y las secuelas de la fijación de la articulación atlanto-axoidea

Grisel syndrome (GS) is a non-traumatic atlanto-axial subluxation produced after an inflammatory, infectious or postsurgical process of the upper neck region. It is a characteristic, although currently uncommon complication of acute bacterial pharyngitis in the pediatric age. Presentation in adults is even more infrequent and requires specific management. We present the case of a 68-year-old patient with a history of chronic myeloid leukemia, who presented with infectious polyarthritis, cervicalgia, torticollis and cervical impotence. Cervical radiography, CT, and MRI showed a C1-C2 subluxation adjacent to a pharyngeal abscess, so GS was diagnosed. After antibiotic therapy, the patient had to undergo surgery due to the failure of the closed reduction. Due to its low incidence, there are no clinical guidelines for the management of these patients; The interdisciplinary collaboration is fundamental to establish the opportune diagnosis that allows to establish the conservative treatment and prevent the surgery, as well as the complications and sequelae of the fixation of the atlanto-axial joint

Atlantoaxial subluxation secondary to retropharyngeal abcess in adults (Grisel's syndrome). Review of literature about a clinical case. / Subluxación atlanto-axoidea secundaria a absceso retrofaríngeo en el adulto (síndrome de Grisel). Revisión de la literatura a propósito de un caso clínico.

Grisel syndrome (GS) is a non-traumatic atlanto-axial subluxation produced after an inflammatory, infectious or postsurgical process of the upper neck region. It is a characteristic, although currently uncommon complication of acute bacterial pharyngitis in the pediatric age. Presentation in adults is even more infrequent and requires specific management. We present the case of a 68-year-old patient with a history of chronic myeloid leukemia, who presented with infectious polyarthritis, cervicalgia, torticollis and cervical impotence. Cervical radiography, CT, and MRI showed a C1-C2 subluxation adjacent to a pharyngeal abscess, so GS was diagnosed. After antibiotic therapy, the patient had to undergo surgery due to the failure of the closed reduction. Due to its low incidence, there are no clinical guidelines for the management of these patients; The interdisciplinary collaboration is fundamental to establish the opportune diagnosis that allows to establish the conservative treatment and prevent the surgery, as well as the complications and sequelae of the fixation of the atlanto-axial joint.

Síndrome de Cola de Caballo asociado a tratamiento quiropráctico: Reporte de 3 casos y revisión de la literatura / Horsetail syndrome associated with chiropractic treatment: Report of 3 cases and review of the literature

El síndrome de cola de caballo (SCC) es una urgencia quirúrgica poco frecuente con una incidencia estimada de hasta 1,8 casos por millón de habitantes, producida por la compresión de las raíces nerviosas en el extremo inferior del canal espinal. La manipulación espinal puede desempeñar un papel etiogénico, provocando la movilización y extrusión del disco. El diagnóstico temprano y el tratamiento oportuno son cruciales, ya que el pronóstico suele ser desfavorable si el tratamiento quirúrgico se retrasa produciendo un daño neurológico permanente. El objetivo de este trabajo es identificar los potenciales factores de riesgo para la manipulación espinal y optimizar esta práctica, evitando así posibles complicaciones derivadas del tratamiento quiropráctico. Presentamos 3 casos de SCC, observados y tratados en nuestro centro, en los que se sugiere una estrecha relación entre la manipulación espinal quiropráctica y la aparición de dicho síndrome. Tras realizarles una RM en la que se observó una hernia discal L5-S1 causante del SCC, los 3 pacientes fueron tratados quirúrgicamente de forma urgente. Los casos presentados demostraron la existencia de una asociación patogénica entre la manipulación espinal y el desarrollo del SCC, al producirse dicho síndrome en las horas siguientes a la manipulación debida a la protusión abrupta de un disco demostrado por RM.

Introduction: Cauda equine syndrome (CES) is a rare surgical emergency with an estimated incidence of up to 1.8 cases per million. It is caused by compression of the nerve roots at the lowest point of the spinal canal. Spinal manipulation can play a pathogenic role, resulting in mobilization and extrusion of the disc. Early diagnosis and timely treatment are crucial, since the prognosis is usually unfavorable and permanent neurological damage likely if surgical treatment is delayed. Objective: The aim of this study was to identify potential risk factors associated with spinal manipulation and, thereby, optimize this practice to reduce the risk of complications from chiropractic treatment. Methods: We present three cases of CES, observed and treated at our center, in which a close relationship between chiropractic spinal manipulation and the appearance of CES was apparent. Results: After magnetic resonance imaging (MRI) revealed an L5-S1 herniated disc causing the SCC, all three patients underwent urgent surgical treatment. Conclusion: The three presented cases demonstrate a strong pathogenic relationship between spinal manipulation and the development of CES, when this syndrome occurs within hours of spinal manipulation, secondary to MRI-documented acute disc protrusion.